目的 探讨周细胞脱失在神经精神性狼疮（NPSLE）中的病理作用及其分子机制，并评估PDGFR-β信号通路作为NPSLE治疗的新靶点。 方法 使用8周龄雌性MRL/lpr小鼠构建NPSLE模型，筛选出表现行为异常的小鼠。通过调节PDGFR-β信号通路，使用激动剂促进周细胞增殖，或使用抑制剂抑制周细胞凋亡，评估其对血脑屏障功能、血瘀证目征、脑组织神经元及紧密连接蛋白的影响。采用伊文思蓝法（EB染色）、HE染色、尼氏染色及免疫荧光染色，分析紧密连接蛋白（Cadherin、ZO-1）、内皮细胞标记（CD31）及周细胞标记（NG2）的表达。 结果 NPSLE组小鼠表现显著的焦虑、抑郁及认知障碍。PDGFR-β抑制组小鼠血瘀证目征评分显著升高（P < 0.01），血脑屏障通透性明显增加（P < 0.001），神经元数量显著减少，紧密连接蛋白表达下降，周细胞脱失加重。相比之下，PDGFR-β激动组小鼠血瘀证目征评分显著降低（P < 0.01），周细胞脱失显著改善，紧密连接蛋白表达增加，神经元损伤减轻，血脑屏障功能恢复（P < 0.001）。免疫荧光染色进一步证实，PDGFR-β激动组在周细胞保护方面有显著改善。 结论 周细胞脱失与血脑屏障通透性增加及血瘀证目征的加重密切相关，PDGFR-β信号通路的调控可能为NPSLE治疗提供新的靶点。

Objective This study aims to investigate the pathological role and molecular mechanisms of pericyte depletion in neuropsychiatric lupus （NPSLE） and to assess the potential of the PDGFR-β signaling pathway as a novel therapeutic target for NPSLE. Methods NPSLE models were established using 8-week-old female MRL/lpr mice， from which those exhibiting abnormal behaviors were selected for further analysis. The PDGFR-β signaling pathway was modulated using an agonist to promote pericyte proliferation or an inhibitor to suppress pericyte apoptosis. The effects of these treatments on blood-brain barrier （BBB） integrity， eye-signs in blood stasis syndrome， neuronal integrity， and tight junction protein expression were evaluated. Evans blue staining， H&E staining， Nissl staining， and immunofluorescence staining were employed to assess the expression of tight junction proteins （Cadherin， ZO-1）， endothelial cell markers （CD31）， and pericyte markers （NG2）. Results Mice in the NPSLE group exhibited significant anxiety， depression， and cognitive impairment. In the PDGFR-β inhibition group， eye-signs in blood stasis syndrome scores were significantly elevated （P < 0.01）， BBB permeability was markedly increased （P < 0.001）， neuronal numbers were significantly reduced， tight junction protein expression was diminished， and pericyte depletion was aggravated. Conversely， the PDGFR-β agonist group showed a significant reduction in eye-signs in blood stasis syndrome scores （P < 0.01）， improved pericyte survival， enhanced expression of tight junction proteins， reduced neuronal damage， and restoration of BBB function （P < 0.001）. Immunofluorescence staining further confirmed that PDGFR-β activation significantly protected pericytes. Conclusions Pericyte depletion is closely associated with increased BBB permeability and exacerbation of eye-signs in blood stasis syndrome. Modulation of the PDGFR-β signaling pathway may provide a promising therapeutic strategy for NPSLE.